Reddy Prabashni, Atay Julie K, Selbovitz Leslie G, Connors Jean Marie, Piazza Gregory, Block Caroline Cole, Arpino Paul A, Berliner Nancy, Hutter Adolph M, Fischer Michael A, Kuter David, Weitzman James, Sherwood Geoffery K, Almozlino Avraham, Giugliano Robert P
Center for Drug Policy, Partners Healthcare, Needham, MA, USA.
Crit Pathw Cardiol. 2011 Sep;10(3):117-27. doi: 10.1097/HPC.0b013e3182315c03.
Dabigatran etexilate is the first commercially available oral direct thrombin inhibitor. A single trial has studied patients at risk for stroke associated with nonvalvular atrial fibrillation; in this trial, dabigatran 150 mg twice a day met the criteria for superiority over warfarin in preventing stroke and systemic embolism while reducing the rate of hemorrhagic stroke with a similar risk of major bleeding. For the treatment of venous thromboembolism, dabigatran 150 mg twice a day had comparable efficacy and safety versus warfarin. In contrast, dabigatran was less effective than enoxaparin 30 mg twice a day in venous thromboembolism prevention in orthopedic surgery. Advantages of dabigatran over warfarin include its lack of need for routine laboratory monitoring, a fixed-dose regimen, and potentially fewer clinically important drug interactions. Concerns include higher incidences of dyspepsia and gastrointestinal bleeding, twice-daily dosing, and lack of effective antidote. Additional drawbacks include higher drug cost versus warfarin, accumulation in case of renal impairment, higher discontinuation rates due to adverse events, and limited long-term safety and trial data. From a payer perspective, overall costs will be higher with dabigatran compared with warfarin, but dabigatran does meet the threshold to be considered a cost-effective therapy. In addition, the lack of need for regular laboratory monitoring is a quality of life advantage for patients on dabigatran. These observations suggest that dabigatran is a valuable addition to the therapeutic armamentarium for stroke prevention in selected patients with atrial fibrillation although caution should be exercised given the limited data on this agent and higher cost.
达比加群酯是首个上市的口服直接凝血酶抑制剂。一项试验研究了有非瓣膜性心房颤动相关卒中风险的患者；在该试验中，每日两次服用150mg达比加群在预防卒中和全身性栓塞方面符合优于华法林的标准，同时降低了出血性卒中发生率，且大出血风险相似。对于静脉血栓栓塞的治疗，每日两次服用150mg达比加群与华法林的疗效和安全性相当。相比之下，在骨科手术中预防静脉血栓栓塞方面，达比加群不如每日两次服用30mg依诺肝素有效。达比加群相对于华法林的优势包括无需常规实验室监测、固定剂量方案以及潜在的临床重要药物相互作用较少。担忧之处包括消化不良和胃肠道出血发生率较高、每日两次给药以及缺乏有效的解毒剂。其他缺点包括与华法林相比药物成本较高、肾功能损害时会蓄积、因不良事件导致停药率较高以及长期安全性和试验数据有限。从支付方角度来看，与华法林相比，达比加群的总体成本会更高，但达比加群确实符合被视为具有成本效益疗法的阈值。此外，无需定期实验室监测对服用达比加群的患者来说是生活质量方面的一个优势。这些观察结果表明，达比加群是用于预防特定心房颤动患者卒中的治疗手段中的一项有价值补充，不过鉴于该药物数据有限且成本较高，应谨慎使用。
